POSITRON-EMISSION-TOMOGRAPHY IN ASYMPTOMATIC GENE CARRIERS OF MACHADO-JOSEPH-DISEASE

Objectives-The metabolic changes in the brain of symptomatic subjects affected with Machado-Joseph disease have been previously documented u sing PET with fluorine-18-fluorodeoxyglucase (FDG). The aim of this st udy was to evaluate these changes in asymptomatic, Machado-Joseph dise ase gene carriers. Methods-Seven asymptomatic Machado-Joseph disease g ene carriers, identified using a molecular test, and 10 normal control subjects were recruited for PET studies using FDG. Regional uptake ra tios of FDG were calculated from the radioactivity of the cerebellar h emispheres, brainstem, and the temporal, parietal and occipital cortic es, divided by the activity in the thalamus. Results-In comparison wit h data obtained from normal control subjects, there was significantly decreased FDG utilisation in the cerebellar hemispheres, brainstem, an d occipital cortex, and increased FDG metabolism in the parietal and t emporal cortices of asymptomatic Machado-Joseph disease: gene carriers , suggesting preclinical disease activity. Discriminant analysis of re gional FDG uptake correctly classified genetic status (Machado-Joseph disease: mutation carriers v mutation negative subjects) in 25 of 25 s ubjects (100% sensitivity and 100% specificity), and clinical status ( asymptomatic mutation carriers v symptomatic patients) in 14 of 15 sub jects (100% sensitivity and 85.7% specificity).Conclusion-Subclinical changes of FDG consumption, as measured by noninvasive PET, can act as an objective marker of preclinical disease activity in Machado-Joseph disease.